ArticleCancer science2015
Multitargeting strategy using lenvatinib and golvatinib: maximizing anti-angiogenesis activity in a preclinical cancer model.
Article in Cancer science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- The integration of immune checkpoint inhibitors with VEGF targeted agents in advanced gastric and gastroesophageal adenocarcinoma: a review on the rationale and results of early phase trials.Journal of hematology & oncology · 2021Pooled it
- S2303: phase II/III trial of paclitaxel + ramucirumab ± nivolumab in gastric and esophageal adenocarcinoma (PARAMUNE).Future oncology (London, England) · 2025Article
- Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.Medical oncology (Northwood, London, England) · 2024Review
- Evaluation of the inhibitory effect of azoles on pharmacokinetics of lenvatinib in rats both in vivo and in vitro by UPLC-MS/MS.Thoracic cancer · 2023Article
- Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma.Frontiers in pharmacology · 2023Review
- Lenvatinib as a salvage therapy for advanced metastatic medullary thyroid cancer.Journal of endocrinological investigation · 2021Article
- New Angiogenic Regulators Produced by TAMs: Perspective for Targeting Tumor Angiogenesis.Cancers · 2021Review
- MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma.Cancers · 2021Review
- Ras Mitogen-activated Protein Kinase Signaling and Kinase Suppressor of Ras as Therapeutic Targets for Hepatocellular Carcinoma.Journal of liver cancer · 2021Review
- The Role of IGF/IGF-1R Signaling in Hepatocellular Carcinomas: Stemness-Related Properties and Drug Resistance.International journal of molecular sciences · 2021Review
- Combination of molecularly targeted therapies and immune checkpoint inhibitors in the new era of unresectable hepatocellular carcinoma treatment.Therapeutic advances in medical oncology · 2021Review
- Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses.Cells · 2020Review
- Antiangiogenesis Roles of Exosomes with Fei-Liu-Ping Ointment Treatment are Involved in the Lung Carcinoma with the Lewis Xenograft Mouse Model.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors.Molecules (Basel, Switzerland) · 2019Article
- Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment.Cancer management and research · 2019Review
- Targeting tumour microenvironment by tyrosine kinase inhibitor.Molecular cancer · 2018Review
- The role of tumor microenvironment in resistance to anti-angiogenic therapy.F1000Research · 2018Review
- Dual roles of protein tyrosine phosphatase kappa in coordinating angiogenesis induced by pro-angiogenic factors.International journal of oncology · 2017Article
- Insights into the therapeutic potential of hypoxia-inducible factor-1α small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes.International journal of nanomedicine · 2016Article
- Hepatocellular Carcinoma: Etiology and Current and Future Drugs.Journal of clinical and experimental hepatologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Almost all cancers show intrinsic and/or evasive resistance to vascular endothelial growth factor (VEGF) inhibitors by multiple mechanisms. Serum angiopoietin-2 (Ang2) level has been proposed as a potential biomarker of VEGF inhibitor response in several cancers. From these clinical observations, the Ang2 and Tie2 (its receptor) axis has been focused on as a promising target. Here, we show a novel strategy to circumvent the resistance by combining multi-tyrosine kinase inhibitors lenvatinib (VEGF receptor, fibroblast growth factor receptor, and RET inhibitor) and golvatinib (E7050; c-Met, Tie2, and EphB4 inhibitor). Tie2 identifies a highly pro-angiogenic macrophage subset, Tie2-expressing macrophages (TEM). Angi-Tie2 and EphB4-EphrinB2 signaling plays critical roles in pericyte-mediated vessel stabilization. In vitro analyses suggested that golvatinib combined with lenvatinib inhibited pericyte-mediated vessel stabilization and TEM differentiation. In thyroid and endometrial cancer models, golvatinib and lenvatinib inhibited pericyte network development and TEM infiltration, resulting in severe perfusion disorder and massive apoptosis. Body weight loss was tolerable, and no macroscopic change was observed. These preclinical studies suggest that modulation of the tumor microenvironment by a strategic and well-tolerated combination of multi-targeting tyrosine kinase inhibitors may sensitize cancer to VEGF inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.